Researchers have recently published a study in Vaccines that examines how the HIV treatment and immune profile affect the body’s ability to fight off the virus by producing antibodies. These antibodies, known as broadly neutralizing antibodies, are important because they can target and neutralize different strains of HIV. This is crucial for developing an effective HIV vaccine, as these antibodies could help create long-lasting protection against the virus. The research was led by Dr. Victor Sanchez-Merino and Dr. Eloisa Yuste, from the National Microbiology Center (ISCIII) in Madrid, Spain. The findings are expected to play a role in advancing HIV-1 vaccine strategies.
Scientists worked with more than two hundred participants, including both adults and children under the age of 15, all of whom had undetectable levels of HIV-1 in their blood thanks to ongoing HIV treatment. The research aimed to find out the potential for both aviremic children and adults to develop broadly neutralizing responses to HIV-1 while emphasizing the importance of antiretroviral timing and immune profile in this process. As Dr. Sanchez-Merino explained, “What we discovered is that neutralization breadth in aviremic individuals is associated with the time to treatment initiation and the CD4+/CD8+ ratio in both children and adults living with HIV-1”.
Results from the study revealed that adults were much better at producing broadly neutralizing antibodies than children. Nearly half of the adults could neutralize several different strains of HIV, while only a small number of children showed the same ability. Researchers believe this is because adults generally start treatment later than children, giving their immune systems more time to be exposed to the virus. In contrast, children typically begin treatment just after infection, limiting their immune systems’ exposure to HIV and reducing their ability to develop these protective antibodies.
Both adults and children showed a link between the ratio of two important immune cells and the strength of their antibody response. When the balance of CD4-positive to CD8-positive cells was lower, participants were more likely to have stronger neutralizing responses. This suggests that having a higher proportion of CD8-positive cells in relation to CD4-positive cells may help the body fight off multiple strains of HIV more effectively. The researchers also noted that other factors, such as the overall length of time someone had been on HIV treatment or the time since they were first infected, didn’t seem to affect their ability to produce these antibodies. This highlights the importance of early immune responses in controlling HIV.
Findings also showed that children who started HIV treatment within a few months of birth had almost no ability to neutralize the virus. This suggests that starting treatment too early might prevent the immune system from developing the ability to recognize and fight off HIV in the future. “We found that children who were infected at birth and began treatment very early often lost the specific antibodies that could help their immune system fight HIV,” said Dr. Yuste. These results highlight the delicate balance between controlling the virus early and allowing the immune system enough exposure to mount a strong defense, providing important clues for improving future HIV treatment and vaccine approaches.
Moving forward, the research team suggests that more studies should be done to understand how long-term exposure to the virus before treatment affects the development of these broadly neutralizing antibodies. In particular, the study emphasized the importance of learning more about how children’s immune systems develop differently from adults, which could lead to better HIV treatments and prevention methods. As Dr. Sanchez-Merino noted, “Our work shows that these important antibody responses can develop even without ongoing exposure to the virus, as long as the immune system is initially exposed to a significant amount of the virus.”
These findings may have a major impact on the development of HIV vaccines. The ability to produce long-lasting antibodies that can fight multiple HIV strains, even without continuous exposure to the virus, could lead to better-designed vaccines. Future strategies might need to carefully consider when and how much of the virus should be introduced to the immune system to create the strongest and most lasting defense, particularly in younger individuals.
Overall, this research indicates that ensuring ample antigenic stimulation prior to initiating ART improves the capacity to produce long-lasting broadly neutralizing responses. This suggests that it is possible to induce these responses without the need for continuous vaccine exposure, as long as the initial antigenic stimulation is robust and sustained. These findings have significant implications for the development of effective vaccination strategies against HIV.
Journal Reference
Sanchez-Merino, V., Martin-Serrano, M., Beltran, M., Lazaro-Martin, B., Cervantes, E., Oltra, M., et al. (2024). “The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios.” Vaccines, 12(8). DOI: https://doi.org/10.3390/vaccines12010008
About the Authors
Víctor Sánchez Merino: Graduated with a bachelor’s degree and PhD in Pharmacy from the Complutense University of Madrid, specializing in virology and molecular biology. His research has focused on the study of HIV and EBV. His doctoral thesis addressed the evolution of HIV-1 and the restoration of the mutant reverse transcriptase function of HIV-1. He completed a postdoctoral stay at Harvard University, researching new viral interactions (2001-2003). At the University of Massachusetts, he explored CD8+ T cell responses in vertical transmission of HIV (2003-2008). In Spain, at the Hospital Clínic-IDIBAPS (Barcelona; 2008-2017) and the Carlos III Health Institute (Madrid; 2017-Present), he has led research on HIV-1 neutralizing antibodies and the design of preventive vaccines. He is currently co-leading with Dr. Eloísa Yuste Herranz, the Humoral Immunity and HIV Vaccines Unit at the National Microbiology Center (Carlos III Health Institute, Madrid, Spain). Additionally, he is a professor and principal investigator at Alfonso X el Sabio University (Madrid).
Eloísa Yuste Herranz: Graduated with a bachelor’s degree and PhD in Biological Sciences from the Complutense University of Madrid. She completed a first postdoctoral stay (1998-2001) at the Severo Ochoa Molecular Biology Center (Madrid). In 2001, she completed a second postdoctoral stay at Harvard Medical School (USA), where she was promoted to Associate Researcher in 2005. In 2008, she joined the August Pi i Sunyer Biomedical Research Institute (Barcelona) as a Ramón y Cajal researcher, and in 2011, she was promoted to I3 Researcher at the same institution. In 2016, she joined the National Center for Microbiology at the Carlos III Health Institute (Madrid) as a Distinguished Researcher. In 2018, she was promoted to Senior Scientist at the same institution. Her research has focused on the study of humoral immunity against HIV-1 and the development of preventive HIV-1 vaccine prototypes. She currently co-leads with Dr. Víctor Sánchez Merino, the Humoral Immunity and HIV Vaccines Unit at the National Microbiology Center (Carlos III Health Institute, Madrid, Spain).
